Children and adolescents with systemic lupus erythematosus and cognitive dysfunction with or without psychosis in a recent small study generally responded well to immunosuppressive treatment lasting at least a year, with little long-term impairment.
Although about half of the patients developed new damage, the new damage did not interfere with their functional abilities, and only 15% of the 53 children in the study had persistent cognitive dysfunction after remission, reported Dr. Lily Siok Hoon Lim and her associates at the Hospital for Sick Children in Toronto.
The study included all children under age 18 years who had SLE (meeting a minimum of 4 of the 11 SLE classification criteria from the American College of Rheumatology) and an SLE-induced psychiatric illness or cognitive dysfunction while being treated at the hospital’s lupus clinic from 1985 to July 2009. Among the cohort of 40 SLE patients with psychiatric disorders and cognitive dysfunction and the 13 with only cognitive dysfunction, the median age at SLE diagnosis was 15 years, and the median age at psychiatric illness diagnosis was 16 years. Most (87%) of the patients were female (J. Rheumatol. 2013 March 1 [doi:10.3899/jrheum.121096]).
The children who were found to suffer cognitive dysfunction as a result of SLE had memory or concentration difficulties and/or academic performance impairments that improved after receiving treatment for the disease. The researchers did not include children whose psychiatric illness was preexisting, was caused by steroids, or was otherwise unrelated to SLE. In addition, none of the patients had comorbidities that may have otherwise accounted for their psychiatric condition or cognitive dysfunction.
All the patients received high-dose steroids and second-line immunosuppressants (except two patients from the earliest time period of the study), primarily azathioprine (60%), intravenous cyclophosphamide (34%), and mycophenolate mofetil (MMF, 2%). During the course of treatment, two patients were switched from azathioprine to MMF, and 10 patients receiving azathioprine were switched to intravenous cyclophosphamide after symptoms worsened. In addition, 16 of the psychiatric patients (42%) received antipsychotic medications for a median of 4.7 months; only 1 patient was still taking this medication a year later.
The patients were evaluated every 2-6 weeks until recovery, but only 49 patients could be assessed for long-term response. Of these, 9 patients (18%) did not respond to the treatment and 40 (82%) did, with a median response time of 39 weeks and no significant difference between the cognitive dysfunction and psychosis groups. The researchers defined response as an absence of all psychiatric and cognitive symptoms after the patient stopped taking antipsychotic medications and was taking less than 50% of the maximum dose of prednisone for at least 3 months.
Another 25 of the responders (63%) went into remission after a median of 71 weeks (72 weeks for the psychiatric group and 70 for the cognitive dysfunction group). Remission was defined as no psychiatric or cognitive symptoms, no antipsychotic medication, and less than 10 mg of prednisone a day or 0.2 mg/kg per day for at least 3 months. Among the 40 responders, 8 patients (20% of the total group) relapsed after a median of 17 weeks, which included 7 of the patients with psychiatric illness and 1 with only cognitive dysfunction.
Of the 51 patients who could be assessed for damage according to the SLE International Collaborative Clinics/American College of Rheumatology Damage Index (SDI), 26 of the patients (52%) had new damage since diagnosis, occurring a median of 0.9 years after diagnosis during a median follow-up time of 1.9 years (range, 0.4-6.5 years). The same proportion of patients with psychosis and cognitive dysfunction, and those with only cognitive dysfunction, had new cognitive impairment (15%) despite treatment during follow-up. There was no significant difference between the two groups in terms of the proportion of patients who had new damage. The most common damage was non–sight-threatening cataract, followed by diabetes, premature ovarian failure, and avascular necrosis. No patients developed chronic psychosis.
Though the researchers noted that the "optimal immunosuppressive treatment for psychiatric SLE is unclear," all the patients who started on cyclophosphamide responded and just over half of the patients started on azathioprine required a switch to cyclophosphamide due to a poor response. "We suggest that pediatric SLE patients with clinically important psychiatric SLE should receive induction therapy with intravenous cyclophosphamide and high-dose prednisone," the authors wrote.
Overall, Dr. Lim’s team found no significant differences between the children with psychosis and those with only cognitive dysfunction in terms of response or remission rates, time to response, relapse rates, or damage accrual.
The study was funded by the Peterborough K.M. Hunter Graduate Studentship, the Joseph M. West Family Memorial Scholarship, the Eddie Steinberg Scholarship Fund, and the Chrisholm Memorial Fellowship, all awarded to Dr. Lim.